Mazar Andrew P
Attenuon LLC, San Diego, California 92121, USA.
Clin Cancer Res. 2008 Sep 15;14(18):5649-55. doi: 10.1158/1078-0432.CCR-07-4863.
The urokinase plasminogen activator receptor (uPAR) has been implicated in the growth, metastasis, and angiogenesis of several solid and hemotologic malignancies. uPAR is part of a cell surface system that also consists of the serine protease uPA and several specific inhibitors (plasminogen activator inhibitors 1 and 2). This system has classically been thought to drive tumor progression by mediating directed extracellular proteolysis on the surface of migrating or invading cells, and intervening with this proteolysis by targeting uPAR has been proposed to represent a novel approach for inhibiting tumor progression. However, despite abundant evidence suggesting the utility of targeting uPAR for the treatment of cancer, there are currently no uPAR-targeted therapies being evaluated in clinical trials. Recent data have provided new insights into the role of uPAR in tumor progression. In addition to mediating proteolysis, this receptor appears to also mediate cell signaling, proliferation, and survival, and these observations have revealed novel ways to target uPAR. How these data have led to a paradigm shift in how the role of uPAR in tumor progression is perceived as well as past and present attempts to therapeutically target a molecule that is generating renewed interest as a cancer target will be discussed in this article.
尿激酶型纤溶酶原激活物受体（uPAR）与多种实体瘤和血液系统恶性肿瘤的生长、转移及血管生成有关。uPAR是细胞表面系统的一部分，该系统还包括丝氨酸蛋白酶uPA和几种特异性抑制剂（纤溶酶原激活物抑制剂1和2）。传统上认为该系统通过介导迁移或侵袭细胞表面的定向细胞外蛋白水解来驱动肿瘤进展，并且有人提出通过靶向uPAR干预这种蛋白水解代表了一种抑制肿瘤进展的新方法。然而，尽管有大量证据表明靶向uPAR可用于癌症治疗，但目前尚无uPAR靶向疗法在临床试验中进行评估。最近的数据为uPAR在肿瘤进展中的作用提供了新的见解。除了介导蛋白水解外，该受体似乎还介导细胞信号传导、增殖和存活，这些观察结果揭示了靶向uPAR的新方法。本文将讨论这些数据如何导致对uPAR在肿瘤进展中作用的认识发生范式转变，以及过去和现在针对作为癌症靶点重新引起人们兴趣的分子进行治疗靶向的尝试。
